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dc.contributor.advisor Hartgerink, Jeffrey D.
dc.creatorO'Leary, Lesley Russell
dc.date.accessioned 2013-03-08T00:37:21Z
dc.date.available 2013-03-08T00:37:21Z
dc.date.issued 2012
dc.identifier.urihttps://hdl.handle.net/1911/70377
dc.description.abstract Replicating the multi-hierarchical self-assembly of collagen (peptide chain to triple helix to nanofiber and, finally, to a hydrogel) has long attracted scientists, both from the fundamental science perspective of supramolecular chemistry and for the potential biomedical applications perceived in tissue engineering. In terms of triple helical formation, collagen is the most abundant protein in the human body with at least 28 types, yet research involving collagen mimetic systems has only recently began to consider the innate ability of collagen to control helix composition and register. Collagen triple helices can be homotrimeric or heterotrimeric and while some types of natural collagen form only one specific composition of helix, others can form multiple. It is critical to fully understand and, if possible, reproduce the control that native collagen has on helix composition and register. In terms of nanofiber formation, many approaches to drive the self-assembly of synthetic systems through the same steps as natural collagen have been partially successful, but none have simultaneously demonstrated all levels of structural assembly. In this work, advancements in the ability to control helix composition and replicate the multi-hierarchical assembly of collagen are described. Both positive and negative design for the assembly of AAB type collagen heterotrimers were utilized by promoting heterotrimer formation though the use of charged amino acids to form intra-helix electrostatic interactions, while simultaneously discouraging homotrimers, resulting in the identification of multiple peptide systems with full control over the composition of the resulting triple helix. Similar salt-bridged hydrogen bonds between charged residues were incorporated into nanofiber forming peptides, one of which successfully assembled into sticky-ended triple helices, nanofibers with characteristic triple helical packing visible in the solution state, and strong hydrogels that are degraded by collagenase at a similar rate to natural collagen. Together, these results provide a better understanding of the self-assembly of collagenous sequences as well as a novel design scheme for synthetic extracellular matrix mimetics with potential applications in regenerative medicine and drug delivery.
dc.format.extent 258 p.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectApplied sciences
Pure sciences
Biological sciences
Self-assembly
Collagen
Nanofibers
Hydrogels
Charged pair interactions
Triple helix
Molecular biology
Biochemistry
Nanoscience
dc.title Multi-Hierarchical Self-Assembly of Collagen Mimetic Peptides into AAB Type Heterotrimers, Nanofibers and Hydrogels Driven by Charged Pair Interactions
dc.identifier.digital OLearyL
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Chemistry
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.identifier.citation O'Leary, Lesley Russell. "Multi-Hierarchical Self-Assembly of Collagen Mimetic Peptides into AAB Type Heterotrimers, Nanofibers and Hydrogels Driven by Charged Pair Interactions." (2012) Diss., Rice University. https://hdl.handle.net/1911/70377.


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